Serum potassium as a predictor of adverse clinical outcomes in patients with increasing comorbidity burden.

AIMS: The aim of this study was to establish whether patients with multiple comorbidities may be at elevated risk of hyperkalaemia (HK), a potentially life-threatening electrolyte imbalance, and the associated adverse clinical outcomes. METHODS AND RESULTS: This was a retrospective, observational cohort study using UK primary and secondary care data. Adult patients with at least one of: resistant hypertension, chronic kidney disease stage 3+, dialysis, heart failure (HF), and diabetes, were eligible for inclusion. According to their diagnoses, patients were grouped into overlapping cohorts that were updated as multimorbidity progressed. Outcomes of interest were incident HK, all-cause mortality (ACM), and major adverse cardiovascular events (MACE). A total of 673 686 patients met the eligibility criteria, 36.3% of whom developed multimorbidity during the study period. A consistent U-shaped association was observed between serum K+ level and adjusted incidence of ACM and MACE. Hyperkalaemia was progressively more common with increasing Charlson Comorbidity Index (CCI). Relative to a CCI <3, scores of ≥3 to <6, and ≥6 were associated with 2.9- and 6.2-fold increases, respectively, in crude HK (serum K+ ≥5.0 mmol/L) incidence rate. In all condition-based cohorts except for HF, there was a clear correlation between increasing CCI and the risk of ACM and MACE associated with hypokalaemia and HK. CONCLUSION: Patients with a higher CCI are at an increased risk of developing HK and appear more prone to adverse clinical outcomes associated with abnormal serum K+ levels, warranting additional routine clinical monitoring.

Risk factors associated with the incidence and recurrence of hyperkalaemia in patients with cardiorenal conditions.

INTRODUCTION: Hyperkalaemia (HK) is associated with increased mortality risk. Prior studies suggest that the causes of HK are multifactorial. This study aimed to examine risk factors for incident and recurrent HK in six large real-world cohorts of UK patients that could be considered at elevated HK risk because of underlying disease pathology and/or medication use. METHODS: This retrospective, observational cohort study utilised UK primary and secondary care data from Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES), respectively. Patients were included if they were aged ≥18 years and had a record of ≥1 condition of interest (chronic kidney disease [CKD] stage 3+, heart failure, resistant hypertension [RHTN], dialysis, diabetes) and/or renin-angiotensin-aldosterone system inhibitors (RAASi) use between 01 January 2003 and 30 June 2018. Based on their diagnosis/ RAASi prescription record, patients were assigned to overlapping cohorts. The outcomes assessed were HK and recurrent HK, the latter defined as second or subsequent HK episode during follow-up. HK was defined as a serum K+ measurement ≥5.0 mmol/L; thresholds of ≥5.5 and ≥ 6.0 mmol/L were also explored. RESULTS: Of 931 460 meeting the eligibility criteria, 310 535 (33.3%) patients experienced ≥1 HK event and 187 719 (20.2%) experienced HK recurrence. The probability of subsequent HK events increased with event number from 60.5% for the second event to 76.5% for the sixth and the corresponding time to the next HK event decreased from 15.8 months to 6.1 months. Amongst the key risk factors, serum creatinine, serum phosphorus, systolic blood pressure, and white cell count demonstrated direct relationships with incidence and recurrence of HK, while inverse relationships were observed for estimated glomerular filtration rate (eGFR), haemoglobin and diastolic blood pressure. The relationship for Charlson's Comorbidity Index was mixed. The use of RAASi and anti-hyperglycaemic agents was associated with an increased risk of HK, while the use of diuretics (non-K+ -sparing) was protective against HK. CONCLUSION: Several risk factors for HK that are easily measured in routine clinical practice were identified, facilitating the identification of patients who are at the highest risk of experiencing HK, including recurrent HK.

Proposed changes to the reimbursement of pharmaceuticals and medical devices in Poland and their impact on market access and the pharmaceutical industry.

In Poland, two proposed amendments to the reimbursement act are currently in preparation; these are likely to substantially change the pricing and reimbursement landscape for both drugs and medical devices. Proposed changes include: alignment of medical device reimbursement with that of pharmaceuticals; relaxing the strict reimbursement criteria for ultra-orphan drugs; establishment of an additional funding category for vaccines; introduction of compassionate use, and a simplified reimbursement pathway for well-established off-label indications; appreciation of manufacturers' innovation and research and development efforts by creating a dedicated innovation budget; introduction of a mechanism preventing excessive parallel import; prolonged duration of reimbursement decisions and reimbursement lists; and increased flexibility in defining drug programmes. Both amendments are still at a draft stage and many aspects of the new regulations remain unclear. Nonetheless, the overall direction of some of the changes is already evident and warrants discussion due to their high expected impact on pharmaceutical and device manufacturers. Here we evaluate the main changes proposed to the reimbursement of drugs, vaccines, and medical devices, and examine the impact they are likely to have on market access and pharmaceutical industry in Poland.